Suicidal behavior and other forms of self-injury are among the most difficult psychiatric problems to treat. Suicide deaths in this country are estimated to be more than 30,000 per year. Suicide attempts are estimated to be 10 times greater than completed suicides. Other forms of non-suicidal self-injurious behaviors such as self- mutilation and trichotillomania, impulsive hair-pulling, are estimated to occur very frequently and can result in significant physical and psychological damage. Most efforts aimed at the identification and treatment of self-injurious behaviors have taken a psychosocial/behavioral slant and it has only been in recent years that a biochemical focus has been applied to these questions. The serotonergic system has been directly or indirectly implicated in the three forms of self-injurious behaviors addressed in this project: 1) attempted suicide; 2) self-mutilation; and 3) trichotillomania. While a substantial body of research now points to a serotonergic dysfunction, there are many questions yet unexamined with regard to serotonin and suicidal behavior. Furthermore, the role of serotonin in self-mutilation and trichotillomania has received very little attention. Previous studies have been narrow in focus, have employed small patient samples, and have usually restricted themselves to a single biochemical measurement to assess the degree of dysfunction in a system. The purpose of this continuation application is twofold: 1) to continue to study serotonergic dysfunction in attempted suicide and build on the findings of our NIMH funded project and 2) to assess the degree to which serotonergic dysfunction is present in two non-suicidal forms of self-injury, i.e., self-mutilation and trichotillomania. Specifically, there are several major issues we wish to address. 1) Are the lower concentrations of 5-HIAA in the CSF of suicide attempters "state" dependent, or do they reflect a biochemical "trait" which may predispose individuals to suicidal behavior? 2) Are there reduced concentrations of CSF 5-HIAA in other forms of self-injurious behavior that are not related to suicidal intent? 3) Are there specific genetic defects in serotonergic receptors in the three forms of self-harm outlined in this proposal? 4) What is the role of a dynamic measure of serotonergic function (fenfluramine challenge) in self-injurious behavior? 5) What is the role of 5-HT(2) binding in platelets? 6) What are the interrelationships among CSF 5-HIAA, fenfluramine -- induced prolactin response and 5-HT(2) binding in the platelet/ 7) Can a genetic component to self-injurious behavior be identified relating to serotonin? This project will be conducted using multiple measures of serotonergic function in three groups of patients who have either attempted suicide, are self-mutilators, or have trichotillomania. The biochemical results from those who self-injure will be compared to those from psychiatric patients who have no history of self-injurious behavior and from normal controls. The findings obtained from this study will help to characterize further the role of serotonin in attempted suicide and other forms of self-injurious behavior and to begin to determine whether there is a genetic defect in serotonergic function related to self-injury. Further, the results of this study may prove valuable in the identification and treatment of those at risk for suicidal behavior and other forms of self-injury.